We have studied the primary genetic response of human peripheral blood T cells to mitogenic activation. By employing subtractive cloning technology, we have previously isolated in excess of 69 genes whose expression is induced within hours of cellular stimulation. Included among these genes are well-known lymphokines, receptors and oncogenes in addition to many novel genes whose functions are suspected to be similarly important for proliferation and the expression of a differentiated T cell phenotype. We have pursued both functional as well as regulatory aspects of several selected novel genes. Two genes encode novel lymphokines which belong to a family of pro-inflammatory factors. We have shown that these genes are among the many cytokines which are inducible by IgE in mast cells. We have localized the lymphokine genes to chromosome 17q, near the loci for von Recklinghausen neurofibromatosis and for acute promyeolocytic leukemia. The two genes are closely linked in the genome in a head to head fashion and we are studying their promoter/enhancer elements. We have done similar studies on the IL-2 and HIV enhancers, which serve as our model systems. We have discovered that an NF-KappaB complex interacting with these enhancers can be activated via cyclosporin A sensitive and insensitive pathways. Three further genes selected for analysis are DNA binding regulatory factors, one of which belongs to the family of steroid receptors and the other two are zinc finger domain containing nuclear proteins. One of the zinc finger proteins is constitutively expressed in all HTLV I or HTLV II transformed cells analyzed to date. We have demonstrated that this gene is transcriptionally induced by the HTLV I tax product and that it is expressed constitutively also in T cells transformed with a herpesvirus saimiri vector carrying tax. Several additional induced and novel genes are under intense investigation, including one encoding a membrane protein of the class II receptor family and another gene with extensive N-terminal homology to the c-rel oncogene and the homeotic gene dorsal of Drosophila.